Misdiagnosis of lymphoma as vasculitis: A case report

Abstract NK/T‐cell lymphoma (NKTCL) is a highly aggressive malignant tumour with a very poor prognosis, which often poses diagnostic difficulties due to the non‐specificity of its clinical presentation. NK/T‐cell lymphoma with eosinophilic hyperplasia syndrome is extremely rare. This article describes a patient with NKTCL misdiagnosed as vasculitis who presented with sinusitis, abdominal pain, anorexia, and lung shadows. Additionally, the patient exhibited extremely high eosinophilia levels, which led to a further misdiagnosis of eosinophilic granuloma. We describe the clinical features, diagnostic methods and differential diagnosis of lymphoma and highlights the importance of a multidisciplinary approach in accurate diagnosis and treatment.


INTRODUCTION
NK/T-cell lymphoma (NKTCL) is frequently overlooked and misdiagnosed due to a lack of specific clinical signs. 1 Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT) is the most common type of NKTCL，which frequently builds up in the nasal cavity, sinuses, nasopharynx, and upper respiratory tract. 2 These symptoms are frequently associated with sustained fever or weight loss, and T-cell lymphomas with hypereosinophilic syndrome are extremely rare. 3

CASE REPORT
The patient is a 52-year-old male, who is a self-employed merchant.He presented to hospital in September 2022 with complaints of abdominal pain, anorexia, and a lung shadow which had been present for more than 3 years.He was diagnosed with 'allergic rhinitis and sinusitis' 5 years ago in a local hospital; however, he didn't receive standardized treatment at that time.Between November 2018 and September 2022, he was seen by Gastroenterology at the local hospital for abdominal pain and anorexia.His peripheral eosinophil count was 3.65 Â 10 9/L, with an 18.7% ratio.His gastroscopy pathology showed moderate chronic gastritis with acute activity as well as moderate atypical hyperplasia of local glandular epithelium.Additionally, eosinophils and neutrophils were present in the bloody exudate from the pancreatic head biopsy.The alveolar septa in the lung tissue were widened, while the stroma was infiltrated by lamellar lymphocytes and a significant number of eosinophils.The final discharge diagnoses were (1) Gastric lesions: eosinophilic gastritis versus Malt lymphoma versus immune gastritis.(2) Chronic pancreatitis.(3) Lung shadow-further investigation required.The patient was prescribed oral prednisone acetate (15-25 mg QD) and proton pump inhibitor for gastric protection.The progression of the patient's condition between 2018 and 2022 is shown in Table 1.
After admission, the patient developed shortness of breath, intermittent fever, abdominal pain.After a multidisciplinary discussion, there was strong suspicion for systemic diseases that affect multiple organs, and eosinophilic granulomatous vasculitis could not be ruled out.The patient received treatment consisting of hydroxyurea, imatinib, cyclophosphamide, and methylprednisolone.However, despite these treatments, the patient's respiratory failure gradually worsened.After high flow nasal canula (FiO 2 60%) support was utilized, his SpO 2 fluctuated between 90% and 95%, with a P/F ratio less than 150.Between October 10 and 27, 2022, he was transferred to the intensive care unit.A right nasal mucosa biopsy was conducted on October 20, 2022.Microscopically, (lateral wall of inferior turbinate, nasal septum, and lateral wall of inferior turbinate) sent mucosal tissue, diffuse infiltration of medium to large tumour cells was seen in the submucosa, the nuclei of the tumour cells were oval, irregularly shaped, with inconspicuous nucleolus, translucent cytoplasm, invading the glandular epithelium, a small number of small lymphocytes, eosinophils, and plasma cells were seen in the background.Immunohistochemical results were as follows (Figure 4): CD20 (small +), CD79a (small +), CD3 (+), CD5 (À), CD4 (+), CD8 (small +), CD56 (À), CD2 (+), Ki67 (40% +), CD10 (+), CD21 (À), CD23 (small +), CXCL-13 (À), and CK (À).In situ hybridisation: EBER (À).Pathology indicated changes in the lateral wall of the inferior turbinate, nasal septum, and lateral wall of the inferior turbinate, and the results revealed non-Hodgkin's lymphoma with a tendency towards nonspecific peripheral T-cell lymphoma.He was treated with Dilizumab and Cedaramine.The final diagnosis was: non-Hodgkin's lymphoma with a tendency towards nonspecific peripheral T-cell lymphoma.Not long after receiving treatment, the patient voluntarily signed off treatment and was discharged due to financial reasons.After follow-up, the patient eventually died of septic shock.
F I G U R E 1 Chest computed tomography showed that multiple lesions in both lungs, suggestive of eosinophilic granulomatosis with polyangiitis (EGPA), eosinophilic pneumonia or fungal infection.Clinical correlation is necessary to make a definitive diagnosis.Multiple slightly enlarged lymph nodes in both lungs and mediastinum, suggestive of reactive hyperplasia.

DISCUSSION
NK/T-cell lymphoma is a subtype of non-Hodgkin's lymphoma that primarily affects extra-nodal organs.Its pathogenesis is not yet fully understood, but it is commonly associated with EBV infection and chronic rhinitis.Other factors, such as genetics and long-term exposure to radiation, may also contribute to its development. 1The lesions in most patients are concentrated in the midline region of the face, particularly in the nasal cavity, and are characterized by disfiguring features.NKTCL is a highly aggressive lymphoma that can rapidly spread to other extranodal sites.Lung involvement can present with various manifestations, such as solid lesions, multiple nodules, and ground-glass shadows, which can be misdiagnosed as pneumonia. 2,3K/T-cell lymphoma with eosinophilia syndrome is a rare condition that can be easily misdiagnosed due to atypical clinical symptoms.
The gold standard for diagnosing NKTCL is histopathological biopsy and immunohistochemical examination.Morphologically, NKTCL is characterized by coagulative necrosis and mixed infiltration of various inflammatory cells, accompanied by prominent proliferation of atypical cells.Tumour cells vary in size and morphology, ranging from small to large cells or anaplastic cells.Tumour cells invade the walls of small blood vessels and surrounding tissues, with fibrinoid necrosis and vasculitis visible in small vessels.The immunophenotype primarily expresses CD56 and CD2, with positivity for cytotoxic markers such as TIA-1, perforin, and granzyme B, while the majority of cells are EBV-positive. 4n clinical practice, NKTCL generally needs to be distinguished from the following diseases: eosinophilic granulomatous polyangiitis (EGPA), chronic sinusitis and lymphomatoid granulomatosis.EGPA is a systemic small and medium-sized vessel necrotizing vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA), which can be accompanied by eosinophil infiltration into tissues.Patients may have a history of asthma, allergic rhinitis, nasal polyps, and so on, and their symptoms can improve after immunosuppressive treatment.Histopathological and immunohistochemical examination are the main methods for differential diagnosis. 5Chronic sinusitis clinical manifestations and imaging findings are non-specific, similar to the early manifestations of ENKTCL-NT.However, most patients can alleviate their symptoms after treatment with nasal drops and antibiotics.Generally, the nasal mucosa of patients is smooth without extensive erosion or scabs.Lymphomatoid granulomatosis is a vascular-centered and vascular-destructive lymphoproliferative disease that preferentially affects extra-nodal sites.It is composed of EB virusinfected B cells mixed with a large number of reactive T cells, and necrosis is common. 6he patient was diagnosed with vasculitis based on early pathological indications of inflammatory lesions, atypical early imaging manifestations, and elevated eosinophils with multisystemic damage.Although the patient did not present with asthma or sinus lesions, the presence of markedly elevated peripheral blood eosinophils, eosinophil infiltration of lung tissue and its small vessel walls, and multisystemic damage including skin rash strongly suggested EGPA. 7This presentation is very rare in patients with NKTCL, so the diagnosis was finally confirmed through pathological biopsy after treatment for vasculitis was ineffective.The cellular morphology of NK/T-cell lymphoma tumour cells is diverse.Tumour necrosis leads to an inflammatory reaction, resulting in the centre of the lesion being mostly necrotic tissue with reactive inflammatory cells.The background of numerous reactive cells can easily blur the infiltration of tumour cells.Diagnosing ENKTCL-NT pathology can be challenging due to small and brittle biopsy samples, few tumour cells, and large necrotic areas.To improve the accuracy of the biopsy, it is recommended to take the biopsy site at the junction of the necrotic foci and the diseased tissues.If necessary, the biopsy should be repeated several times and taken at multiple points.Additionally, the tissue block should be large enough.
The diagnosis, treatment, and learning process of this case have highlighted the importance of early MDT (multidisciplinary team) discussion for diseases with unknown aetiology and multi-system damage.This approach allows for a comprehensive search for the aetiology from multiple perspectives, enabling precise treatment.
Evolution of the patient's condition.
T A B L E 1